Measles, which is accompanied by marked abnormalities of cellular immune function, remains a major cause of childhood mortality. Infection with vaccine strains is associated with similar abnormalities in immune responses. Cross-regulating functional subsets of CD4 T cells have been distinguished by their cytokine profiles: Th1 cells, producing primarily IFN-gamma and IL-2, are important in the development of cell-mediated immunity, and Th2 cells, producing primarily IL-4, IL-5, IL-6, and IL-10, are important in the development of antibody-mediated immunity. With the recent generalization of these phenotyped to CD8 T cells, such cellular subsets and the response pathways that they define, are better termed T1 and T2. T1 responses can be greatly decreased in the presence of a strong coexisting T2 response. The immune functions suppressed in measles are T1 responses, or functions critically dependent upon such responses. There is also preliminary evidence of a shift to T2 responses in both wild-type and vaccine infections. In this proposal we plan to test the hypothesis that the immunosuppression of measles is due to strong dominance of the T2 pathway by characterizing the cytokine phenotypes and functional activities of CD4 and CD8 T cells in natural measles infection and in infection with vaccine virus, and through the identification of immunoregulatory events critical to the generation of the observed cytokine profiles.